Potentiation of spinal glutamatergic response in the neuron-glia interactions underlies the intrathecal IL-1[beta]-induced thermal hyperalgesia in rats

Summary Aims We previously demonstrated that intrathecal IL-1[beta] upregulated phosphorylation of p38 mitogen-activated protein kinase (P-p38 MAPK) and inducible nitric oxide synthase (iNOS) in microglia and astrocytes in spinal cord, increased nitric oxide (NO) release into cerebrospinal fluid, an...

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Veröffentlicht in:CNS neuroscience & therapeutics 2017-07, Vol.23 (7), p.580
Hauptverfasser: Sung, Chun-Sung, Wen, Zhi-Hong, Feng, Chien-Wei, Chen, Chun-Hong, Huang, Shi-Ying, Chen, Nan-Fu, Chen, Wu-Fu, Wong, Chih-Shung
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container_end_page
container_issue 7
container_start_page 580
container_title CNS neuroscience & therapeutics
container_volume 23
creator Sung, Chun-Sung
Wen, Zhi-Hong
Feng, Chien-Wei
Chen, Chun-Hong
Huang, Shi-Ying
Chen, Nan-Fu
Chen, Wu-Fu
Wong, Chih-Shung
description Summary Aims We previously demonstrated that intrathecal IL-1[beta] upregulated phosphorylation of p38 mitogen-activated protein kinase (P-p38 MAPK) and inducible nitric oxide synthase (iNOS) in microglia and astrocytes in spinal cord, increased nitric oxide (NO) release into cerebrospinal fluid, and induced thermal hyperalgesia in rats. This study investigated the role of spinal glutamatergic response in intrathecal IL-1[beta]-induced nociception in rats. Methods The pretreatment effects of MK-801 (5 µg), minocycline (20 µg), and SB203580 (5 µg) on intrathecal IL-1[beta] (100 ng) in rats were measured by behavior, Western blotting, CSF analysis, and immunofluorescence studies. Results IL-1[beta] increased phosphorylation of NR-1 (p-NR1) subunit of N-methyl-D-aspartate receptors in neurons and microglia, reduced glutamate transporters (GTs; glutamate/aspartate transporter by 60.9%, glutamate transporter-1 by 55.0%, excitatory amino acid carrier-1 by 39.8%; P
doi_str_mv 10.1111/cns.12705
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This study investigated the role of spinal glutamatergic response in intrathecal IL-1[beta]-induced nociception in rats. Methods The pretreatment effects of MK-801 (5 µg), minocycline (20 µg), and SB203580 (5 µg) on intrathecal IL-1[beta] (100 ng) in rats were measured by behavior, Western blotting, CSF analysis, and immunofluorescence studies. Results IL-1[beta] increased phosphorylation of NR-1 (p-NR1) subunit of N-methyl-D-aspartate receptors in neurons and microglia, reduced glutamate transporters (GTs; glutamate/aspartate transporter by 60.9%, glutamate transporter-1 by 55.0%, excitatory amino acid carrier-1 by 39.8%; P&lt;.05 for all), and increased glutamate (29%-133% increase from 1.5 to 12 hours; P&lt;.05) and NO (44%-101% increase from 4 to 12 hours; P&lt;.05) levels in cerebrospinal fluid. MK-801 significantly inhibited all the IL-1[beta]-induced responses; however, minocycline and SB203580 blocked the IL-1[beta]-downregulated GTs and elevated glutamate but not the upregulated p-NR1. Conclusion The enhanced glutamatergic response and neuron-glia interaction potentiate the intrathecal IL-1[beta]-activated P-p38/iNOS/NO signaling and thermal hyperalgesia.</description><identifier>ISSN: 1755-5930</identifier><identifier>EISSN: 1755-5949</identifier><identifier>DOI: 10.1111/cns.12705</identifier><language>eng</language><publisher>Oxford: John Wiley &amp; Sons, Inc</publisher><subject>Amino acids ; Astrocytes ; Cerebrospinal fluid ; Dizocilpine ; Glutamatergic transmission ; Glutamic acid receptors ; Glutamic acid transporter ; Hyperalgesia ; Immunofluorescence ; Interleukin 1 ; Kinases ; MAP kinase ; Microglia ; Minocycline ; N-Methyl-D-aspartic acid receptors ; Neuronal-glial interactions ; Nitric oxide ; Nitric-oxide synthase ; Pain perception ; Phosphorylation ; Potentiation ; Protein kinase ; Rodents ; Spinal cord ; Western blotting</subject><ispartof>CNS neuroscience &amp; therapeutics, 2017-07, Vol.23 (7), p.580</ispartof><rights>Copyright © 2017 John Wiley &amp; Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Sung, Chun-Sung</creatorcontrib><creatorcontrib>Wen, Zhi-Hong</creatorcontrib><creatorcontrib>Feng, Chien-Wei</creatorcontrib><creatorcontrib>Chen, Chun-Hong</creatorcontrib><creatorcontrib>Huang, Shi-Ying</creatorcontrib><creatorcontrib>Chen, Nan-Fu</creatorcontrib><creatorcontrib>Chen, Wu-Fu</creatorcontrib><creatorcontrib>Wong, Chih-Shung</creatorcontrib><title>Potentiation of spinal glutamatergic response in the neuron-glia interactions underlies the intrathecal IL-1[beta]-induced thermal hyperalgesia in rats</title><title>CNS neuroscience &amp; therapeutics</title><description>Summary Aims We previously demonstrated that intrathecal IL-1[beta] upregulated phosphorylation of p38 mitogen-activated protein kinase (P-p38 MAPK) and inducible nitric oxide synthase (iNOS) in microglia and astrocytes in spinal cord, increased nitric oxide (NO) release into cerebrospinal fluid, and induced thermal hyperalgesia in rats. This study investigated the role of spinal glutamatergic response in intrathecal IL-1[beta]-induced nociception in rats. Methods The pretreatment effects of MK-801 (5 µg), minocycline (20 µg), and SB203580 (5 µg) on intrathecal IL-1[beta] (100 ng) in rats were measured by behavior, Western blotting, CSF analysis, and immunofluorescence studies. Results IL-1[beta] increased phosphorylation of NR-1 (p-NR1) subunit of N-methyl-D-aspartate receptors in neurons and microglia, reduced glutamate transporters (GTs; glutamate/aspartate transporter by 60.9%, glutamate transporter-1 by 55.0%, excitatory amino acid carrier-1 by 39.8%; P&lt;.05 for all), and increased glutamate (29%-133% increase from 1.5 to 12 hours; P&lt;.05) and NO (44%-101% increase from 4 to 12 hours; P&lt;.05) levels in cerebrospinal fluid. MK-801 significantly inhibited all the IL-1[beta]-induced responses; however, minocycline and SB203580 blocked the IL-1[beta]-downregulated GTs and elevated glutamate but not the upregulated p-NR1. Conclusion The enhanced glutamatergic response and neuron-glia interaction potentiate the intrathecal IL-1[beta]-activated P-p38/iNOS/NO signaling and thermal hyperalgesia.</description><subject>Amino acids</subject><subject>Astrocytes</subject><subject>Cerebrospinal fluid</subject><subject>Dizocilpine</subject><subject>Glutamatergic transmission</subject><subject>Glutamic acid receptors</subject><subject>Glutamic acid transporter</subject><subject>Hyperalgesia</subject><subject>Immunofluorescence</subject><subject>Interleukin 1</subject><subject>Kinases</subject><subject>MAP kinase</subject><subject>Microglia</subject><subject>Minocycline</subject><subject>N-Methyl-D-aspartic acid receptors</subject><subject>Neuronal-glial interactions</subject><subject>Nitric oxide</subject><subject>Nitric-oxide synthase</subject><subject>Pain perception</subject><subject>Phosphorylation</subject><subject>Potentiation</subject><subject>Protein kinase</subject><subject>Rodents</subject><subject>Spinal cord</subject><subject>Western blotting</subject><issn>1755-5930</issn><issn>1755-5949</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNo9kE1OwzAQhS0EEqWw4AaWWKfYTuwkS1TxU6kSLGCFUDVxJqmr1A62s-AkXBe3IGYzo3nvfdIMIdecLXiqW23DgouSyRMy46WUmayL-vR_ztk5uQhhx5gSVV3NyPeLi2ijgWicpa6jYTQWBtoPU4Q9RPS90dRjGJ0NSI2lcYvU4uSdzfrBQFolE-hDPtDJtugHg-FoS5KHNOgEXK0z_t5ghI_M2HbS2B4sfp-k7deYCEOP4YijKRMuyVkHQ8Crvz4nbw_3r8unbP38uFrerbOR8zxmJTSl7tItuZZ1pSoNoqqg6xoJvFO1LpWCUpRKi7ZAhW0jgLcArGg0l4JBPic3v9zRu88JQ9zs3OTTB8KG15zJvBCK5z-7jGx4</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Sung, Chun-Sung</creator><creator>Wen, Zhi-Hong</creator><creator>Feng, Chien-Wei</creator><creator>Chen, Chun-Hong</creator><creator>Huang, Shi-Ying</creator><creator>Chen, Nan-Fu</creator><creator>Chen, Wu-Fu</creator><creator>Wong, Chih-Shung</creator><general>John Wiley &amp; Sons, Inc</general><scope>7TK</scope><scope>K9.</scope></search><sort><creationdate>20170701</creationdate><title>Potentiation of spinal glutamatergic response in the neuron-glia interactions underlies the intrathecal IL-1[beta]-induced thermal hyperalgesia in rats</title><author>Sung, Chun-Sung ; Wen, Zhi-Hong ; Feng, Chien-Wei ; Chen, Chun-Hong ; Huang, Shi-Ying ; Chen, Nan-Fu ; Chen, Wu-Fu ; Wong, Chih-Shung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p113t-7ab7cf6283c59868ca288affb5a1f69c766a7276c2d4e6edb2a1daa04bc1520a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Amino acids</topic><topic>Astrocytes</topic><topic>Cerebrospinal fluid</topic><topic>Dizocilpine</topic><topic>Glutamatergic transmission</topic><topic>Glutamic acid receptors</topic><topic>Glutamic acid transporter</topic><topic>Hyperalgesia</topic><topic>Immunofluorescence</topic><topic>Interleukin 1</topic><topic>Kinases</topic><topic>MAP kinase</topic><topic>Microglia</topic><topic>Minocycline</topic><topic>N-Methyl-D-aspartic acid receptors</topic><topic>Neuronal-glial interactions</topic><topic>Nitric oxide</topic><topic>Nitric-oxide synthase</topic><topic>Pain perception</topic><topic>Phosphorylation</topic><topic>Potentiation</topic><topic>Protein kinase</topic><topic>Rodents</topic><topic>Spinal cord</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sung, Chun-Sung</creatorcontrib><creatorcontrib>Wen, Zhi-Hong</creatorcontrib><creatorcontrib>Feng, Chien-Wei</creatorcontrib><creatorcontrib>Chen, Chun-Hong</creatorcontrib><creatorcontrib>Huang, Shi-Ying</creatorcontrib><creatorcontrib>Chen, Nan-Fu</creatorcontrib><creatorcontrib>Chen, Wu-Fu</creatorcontrib><creatorcontrib>Wong, Chih-Shung</creatorcontrib><collection>Neurosciences Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><jtitle>CNS neuroscience &amp; therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sung, Chun-Sung</au><au>Wen, Zhi-Hong</au><au>Feng, Chien-Wei</au><au>Chen, Chun-Hong</au><au>Huang, Shi-Ying</au><au>Chen, Nan-Fu</au><au>Chen, Wu-Fu</au><au>Wong, Chih-Shung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potentiation of spinal glutamatergic response in the neuron-glia interactions underlies the intrathecal IL-1[beta]-induced thermal hyperalgesia in rats</atitle><jtitle>CNS neuroscience &amp; therapeutics</jtitle><date>2017-07-01</date><risdate>2017</risdate><volume>23</volume><issue>7</issue><spage>580</spage><pages>580-</pages><issn>1755-5930</issn><eissn>1755-5949</eissn><abstract>Summary Aims We previously demonstrated that intrathecal IL-1[beta] upregulated phosphorylation of p38 mitogen-activated protein kinase (P-p38 MAPK) and inducible nitric oxide synthase (iNOS) in microglia and astrocytes in spinal cord, increased nitric oxide (NO) release into cerebrospinal fluid, and induced thermal hyperalgesia in rats. This study investigated the role of spinal glutamatergic response in intrathecal IL-1[beta]-induced nociception in rats. Methods The pretreatment effects of MK-801 (5 µg), minocycline (20 µg), and SB203580 (5 µg) on intrathecal IL-1[beta] (100 ng) in rats were measured by behavior, Western blotting, CSF analysis, and immunofluorescence studies. Results IL-1[beta] increased phosphorylation of NR-1 (p-NR1) subunit of N-methyl-D-aspartate receptors in neurons and microglia, reduced glutamate transporters (GTs; glutamate/aspartate transporter by 60.9%, glutamate transporter-1 by 55.0%, excitatory amino acid carrier-1 by 39.8%; P&lt;.05 for all), and increased glutamate (29%-133% increase from 1.5 to 12 hours; P&lt;.05) and NO (44%-101% increase from 4 to 12 hours; P&lt;.05) levels in cerebrospinal fluid. MK-801 significantly inhibited all the IL-1[beta]-induced responses; however, minocycline and SB203580 blocked the IL-1[beta]-downregulated GTs and elevated glutamate but not the upregulated p-NR1. Conclusion The enhanced glutamatergic response and neuron-glia interaction potentiate the intrathecal IL-1[beta]-activated P-p38/iNOS/NO signaling and thermal hyperalgesia.</abstract><cop>Oxford</cop><pub>John Wiley &amp; Sons, Inc</pub><doi>10.1111/cns.12705</doi><oa>free_for_read</oa></addata></record>
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subjects Amino acids
Astrocytes
Cerebrospinal fluid
Dizocilpine
Glutamatergic transmission
Glutamic acid receptors
Glutamic acid transporter
Hyperalgesia
Immunofluorescence
Interleukin 1
Kinases
MAP kinase
Microglia
Minocycline
N-Methyl-D-aspartic acid receptors
Neuronal-glial interactions
Nitric oxide
Nitric-oxide synthase
Pain perception
Phosphorylation
Potentiation
Protein kinase
Rodents
Spinal cord
Western blotting
title Potentiation of spinal glutamatergic response in the neuron-glia interactions underlies the intrathecal IL-1[beta]-induced thermal hyperalgesia in rats
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